There was a time when hitting 100 years of age meant you'd make the local news. Now, you'd be lucky to squeeze in between the growing crowd of fellow centenarians. Indeed, the number of centenarians is rising in many countries.
Longevity studies point to many common factors, most of which boil down to advantaged genes and healthy lifestyles. More recently, microbiologists have observed that the longevity of centenarians may be associated with unique features in their gut microbiota.
An expanding body of research indicates a connection between aging and the gut microbiome. Because it plays a crucial role in overall health, the gut microbiome reveals insights into the differences in aging and presents opportunities for promoting a longer, healthier life.
This article will describe the relationship between the gut microbiome and extreme aging in addition to the potential of probiotics in extending the human lifespan.
Centenarians, a snapshot
The world is home to nearly one million centenarians, according to a 2024 U.S. Census Bureau International Database. Five countries host more than half of these super-agers. Japan leads the world with 146,000 or 12 of every 10,000 citizens. The United States follows 108,000 or 3 of every 10,000. China, India, and Thailand round out the top five in sheer numbers. Other areas called Blue Zones boast pockets of long-lived people that have been extensively studied.
A 2024 systematic review of 34 studies revealed that 75% of centenarians were female. (Women live longer than men for reasons attributed to an interaction of biological, social, and healthcare factors.)
In general, the key to most successful aging is a healthy lifestyle: plant-based diets, exercise, ample sleep, low stress, and avoiding tobacco and excess alcohol. Maintaining a social life and a positive outlook helps.
Genetics are thought to play a role too with 100 candidate genes potentially involved in human longevity.
Gut microbiome and aging
In 1907, Elie Metchnikoff suggested that health could be improved and aging delayed by altering the gut microbiome with beneficial bacteria from yogurt. His work laid the groundwork for both probiotics and gerontology.
A century of research since has established that the multifarious aging process involves numerous biological activities, influenced by genetic factors, lifestyle, and other elements. Indeed, the gut microbiome fluctuates during different stages of life, with infancy and old age exhibiting the most deviations.
Recent research has shown that aging in humans gradually alters gut microbiota, leading to reduced species diversity, increased inter-individual variations, higher levels of Proteobacteria, and fewer beneficial bacteria such as Bifidobacterium.
The reduction of beneficial microbes, especially those that support mucin production and produce short-chain fatty acids (SCFAs), seems critical in triggering inflammation, weakening the intestinal barrier, and increasing gut permeability, leading to endotoxemia, inflammaging, and aging-related diseases.
Whether these microbiota changes are a cause or effect of aging remains unclear, a distinction crucial for determining the role of microbiome modulation in aging.
As people age they are more likely to use medications, eat differently, exercise less, and live in long-term facilities—all of which can impact gut microbiota negatively. These perturbations are associated with greater susceptibility to infections and compromised gut mucosal barrier integrity. Dysbiosis in the elderly may modulate the immune system, driving chronic low-grade inflammation—called “inflammaging”—which can further distress the function of the gut microbiota. Systemic chronic inflammation is “accompanied by cellular senescence, immunosenescence, organ dysfunction, and age-related diseases.” For example, these changes may contribute to the development and progression of metabolic diseases common in the elderly, such as obesity, insulin resistance, fatty liver, and cardiovascular diseases. The aging microbiome can also affect the gut-brain axis, potentially leading to neurological disorders.
Next up, some good news.
Studies on centenarians
While aging increases susceptibility to numerous chronic and infectious diseases, healthy centenarians are notable exceptions.
Researchers have investigated the gut microbiomes of centenarians to determine if they have unique features. The microbiota composition in centenarians is likely shaped by a combination of genetics, environmental factors, diet, and lifestyle choices.
Research on Sardinian centenarians reveals that their unique gut microbiota, influenced by their isolated environment and Mediterranean diet, differs significantly from younger and other elderly populations, with a higher presence of beneficial bacteria like Bifidobacterium adolescentis and Methanobrevibacter smithii. These bacteria are known to influence key metabolic processes, including the production of short-chain fatty acids (SCFAs), which are beneficial for intestinal health and immune regulation.
Also in Italy, a small group of centenarians was found to have enriched amounts of beneficial bacteria such as Bifidobacterium and Akkermansia muciniphila upon fecal analysis.
A study comparing the gut microbiomes of Estonian centenarians with younger cohorts revealed a significant increase in beneficial Bifidobacterium spp., such as B. dentium and B. longum, in centenarians.
Many more studies have shown that individuals who reach 100+ years of age in relatively good health tend to have a gut microbiota with greater diversity and higher levels of beneficial microbes. It appears that in extreme longevity, the gut microbiota remodels or adapts to counteract a harmful loss of diversity and abundance towards a more healthful composition.
Probiotics, intervention studies
Interventions with probiotics to remodel the gut microbiota have proven beneficial in healthful aging. Infections, diarrhea, inflammatory disorders, and other conditions have shown improvement in studies using probiotics in the elderly.
Probiotics may be actionable in myriad ways: mitigating inflammatory stress, enhancing immune function, reducing immunosenescence, reducing insulin resistance, strengthening mucosal barriers, regulating lipid metabolism, and elevating short-chain fatty acids.
The distinct microbial profiles seen in centenarian research suggest that interventions to modulate the gut microbiota may promote longevity.
Numerous studies have been conducted to ascertain the impact of probiotics/prebiotics/synbiotics/postbiotics and dietary strategies on the gut microbiota and its changes caused by aging or age-related diseases.
Animal studies
When it comes to improving longevity, probiotic supplementation has shown promising results in extending lifespan in experimental animals.
In mice, the probiotic Bifidobacterium animalis subsp. lactis increased survival rates and reduced inflammation and age-related gene expression.
In the nematode, Caenorhabditis elegans (C. elegans)—a worm model used for many aging studies—strains of Ligilactobacillus salivarius and Bacillus licheniformis extended lifespan through dietary restriction and serotonin signaling, respectively, while Lactobacillus gasseri improved oxidative stress resistance. Limosilactobacillus fermentum increased the resistance of C. elegans to foodborne pathogens and extended their lifespan through the mediation of a nuclear hormone receptor family and PMK-1 signaling. Lacticaseibacillus rhamnosus increased the lifespan of C. elegans by about 20% and this was linked to changes in the DAF-16/insulin-like pathway.
In the common fruit fly Drosophila melanogaster, a novel probiotic formulation consisting of Lactiplantibacillus plantarum, Limosilactobacillus fermentum, and B. longum subsp. infantis extended longevity by managing insulin resistance, energy regulation, and reducing oxidative stress and inflammation.
Studies in both experimental animals and human subjects have shown that probiotic bacteria can alter some of the deleterious aspects of immunosenescence. However, animal studies suggest that probiotics can influence the progression and severity of cell senescence.
Human studies
Humans are much more complicated to study than rodents, nematodes, or fruit flies, so it's hard to know if probiotics are extending our lifespan. However, probiotics are already helping people stay healthier as they age. Their anti-inflammatory, antioxidant, and immune-modulating effects suggest they might help slow down the aging process, particularly by reducing stress on cells caused by oxidation. Thus, while it remains to be shown whether probiotics make us live longer, they do enable us to live healthy longer.
Takeaway
The number of people living to 100 is rising, linked to genetics and healthy lifestyles. Recent studies show that centenarians have unique gut microbiota, suggesting a connection between gut health and longevity. Probiotics, known for their anti-inflammatory and antioxidant benefits, may help extend healthy years by positively influencing the gut microbiome. Animal studies have also shown that probiotics can extend lifespan, indicating their potential in promoting longer, healthier lives in humans.
However, much remains to be understood about the influence of the gut microbiome on age-related processes, especially regarding the potential effectiveness of gut-targeted interventions.
Key references
- Baum, Fran et al. “New Perspective on Why Women Live Longer Than Men: An Exploration of Power, Gender, Social Determinants, and Capitals.” International journal of environmental research and public health vol. 18,2 661. 14 Jan. 2021, doi:10.3390/ijerph18020661
- Biagi, Elena et al. “Gut Microbiota and Extreme Longevity.” Current biology : CB vol. 26,11 (2016): 1480-5. doi:10.1016/j.cub.2016.04.016
- Boyajian, Jacqueline Lena et al. “Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity, Skin Health and Cellular Senescence.” Nutrients vol. 13,12 4550. 18 Dec. 2021, doi:10.3390/nu13124550
- Buford, Thomas W. “(Dis)Trust your gut: the gut microbiome in age-related inflammation, health, and disease.”Microbiome vol. 5,1 80. 14 Jul. 2017, doi:10.1186/s40168-017-0296-0
- Caruso, Maria Giovanna et al. “Ageing, Cognitive Decline, and Effects of Physical Exercise: Complexities, and Considerations from Animal Models.” Brain plasticity (Amsterdam, Netherlands) vol. 9,1-2 43-73. 14 May. 2024, doi:10.3233/BPL-230157
- Coman, Vasile, and Dan Cristian Vodnar. “Gut microbiota and old age: Modulating factors and interventions for healthy longevity.” Experimental gerontology vol. 141 (2020): 111095. doi:10.1016/j.exger.2020.111095
- Dai, Zhaoli et al. “A systematic review of diet and medication use among centenarians and near-centenarians worldwide.”GeroScience, 10.1007/s11357-024-01247-4. 5 Jul. 2024, doi:10.1007/s11357-024-01247-4
- Fülöp, Tamas et al. “The Role of Immunosenescence in the Development of Age-Related Diseases.” Revista de investigacion clinica; organo del Hospital de Enfermedades de la Nutricion vol. 68,2 (2016): 84-91.
- Grompone, Gianfranco et al. “Anti-inflammatory Lactobacillus rhamnosus CNCM I-3690 strain protects against oxidative stress and increases lifespan in Caenorhabditis elegans.” PloS one vol. 7,12 (2012): e52493. doi:10.1371/journal.pone.0052493
- Kim, Sangkyu, and S Michal Jazwinski. “The Gut Microbiota and Healthy Aging: A Mini-Review.” Gerontology vol. 64,6 (2018): 513-520. doi:10.1159/000490615
- Li, Xia et al. “Inflammation and aging: signaling pathways and intervention therapies.” Signal transduction and targeted therapy vol. 8,1 239. 8 Jun. 2023, doi:10.1038/s41392-023-01502-8
- Lozada-Martinez, Ivan David et al. “Gut microbiota in centenarians: A potential metabolic and aging regulator in the study of extreme longevity.” Aging medicine (Milton (N.S.W)) vol. 7,3 406-413. 14 Jun. 2024, doi:10.1002/agm2.12336
- Mackowiak, Philip A. “Recycling metchnikoff: probiotics, the intestinal microbiome and the quest for long life.” Frontiers in public health vol. 1 52. 13 Nov. 2013, doi:10.3389/fpubh.2013.00052
- Matsumoto, Mitsuharu et al. “Longevity in mice is promoted by probiotic-induced suppression of colonic senescence dependent on upregulation of gut bacterial polyamine production.” PloS one vol. 6,8 (2011): e23652. doi:10.1371/journal.pone.0023652
- Nagpal, R et al. “Gut microbiota in health and disease: an overview focused on metabolic inflammation.” Beneficial microbes vol. 7,2 (2016): 181-94. doi:10.3920/bm2015.0062
- Nagpal, Ravinder et al. “Gut microbiome and aging: Physiological and mechanistic insights.” Nutrition and healthy aging vol. 4,4 267-285. 15 Jun. 2018, doi:10.3233/NHA-170030
- Nakagawa, Hisako et al. “Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans.”Aging cell vol. 15,2 (2016): 227-36. doi:10.1111/acel.12431
- O'Toole, Paul W, and Ian B Jeffery. “Gut microbiota and aging.” Science (New York, N.Y.) vol. 350,6265 (2015): 1214-5. doi:10.1126/science.aac8469
- O'Toole, Paul W. “Ageing, microbes and health.” Microbial biotechnology vol. 17,5 (2024): e14477. doi:10.1111/1751-7915.14477
- Park, Mi Ri et al. “Bacillus licheniformis Isolated from Traditional Korean Food Resources Enhances the Longevity of Caenorhabditis elegans through Serotonin Signaling.” Journal of agricultural and food chemistry vol. 63,47 (2015): 10227-33. doi:10.1021/acs.jafc.5b03730
- Park, Mi Ri et al. “Probiotic Lactobacillus fermentum strain JDFM216 stimulates the longevity and immune response of Caenorhabditis elegans through a nuclear hormone receptor.” Scientific reports vol. 8,1 7441. 10 May. 2018, doi:10.1038/s41598-018-25333-8
- Ragonnaud, Emeline, and Arya Biragyn. “Gut microbiota as the key controllers of "healthy" aging of elderly people.” Immunity & ageing : I & A vol. 18,1 2. 5 Jan. 2021, doi:10.1186/s12979-020-00213-w
- Santacroce, Luigi et al. “Healthy Diets and Lifestyles in the World: Mediterranean and Blue Zone People Live Longer. Special Focus on Gut Microbiota and Some Food Components.” Endocrine, metabolic & immune disorders drug targets, 10.2174/0118715303271634240319054728. 2 Apr. 2024, doi:10.2174/0118715303271634240319054728
- Sepp, Epp et al. “Comparative Analysis of Gut Microbiota in Centenarians and Young People: Impact of Eating Habits and Childhood Living Environment.” Frontiers in cellular and infection microbiology vol. 12 851404. 15 Mar. 2022, doi:10.3389/fcimb.2022.851404
- Sharma, Rohit, and Yogendra Padwad. “Probiotic bacteria as modulators of cellular senescence: emerging concepts and opportunities.” Gut microbes vol. 11,3 (2020): 335-349. doi:10.1080/19490976.2019.1697148
- Strasser, Barbara et al. “The Effects of Lifestyle and Diet on Gut Microbiota Composition, Inflammation and Muscle Performance in Our Aging Society.” Nutrients vol. 13,6 2045. 15 Jun. 2021, doi:10.3390/nu13062045
- Tsai, Ying-Chieh et al. “Gerobiotics: probiotics targeting fundamental aging processes.” Bioscience of microbiota, food and health vol. 40,1 (2021): 1-11. doi:10.12938/bmfh.2020-026
- Vaiserman, Alexander M et al. “Gut microbiota: A player in aging and a target for anti-aging intervention.” Ageing research reviews vol. 35 (2017): 36-45. doi:10.1016/j.arr.2017.01.001
- Westfall, Susan et al. “Longevity extension in Drosophila through gut-brain communication.” Scientific reports vol. 8,1 8362. 30 May. 2018, doi:10.1038/s41598-018-25382-z
- Wu, Lu et al. “A Cross-Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians.” mSystems vol. 4,4 e00325-19. 9 Jul. 2019, doi:10.1128/mSystems.00325-19
- Xiao, Yue et al. “Achieving healthy aging through gut microbiota-directed dietary intervention: Focusing on microbial biomarkers and host mechanisms.” Journal of advanced research, S2090-1232(24)00092-4. 9 Mar. 2024, doi:10.1016/j.jare.2024.03.005
- Zhao, Yang et al. “Lactobacillus salivarius strain FDB89 induced longevity in Caenorhabditis elegans by dietary restriction.” Journal of microbiology (Seoul, Korea) vol. 51,2 (2013): 183-8. doi:10.1007/s12275-013-2076-2
The International Probiotics Association (IPA) is a global non-profit organization that advocates for the safe and efficacious use of Pre-, Pro- and Post- biotics. The association brings together the knowledge and resources of scientists, healthcare professionals, academics, and regulators to define clear standards that advance the quality of these biotic categories around the world. Holding NGO status before Codex Alimentarius and observer status at ISO, the IPA is also recognized as the unified “Global Voice of Pre-, Pro- and Post- biotics®” around the world. For more information visit: https://internationalprobiotics.org/home/
Clare Fleishman, MS RDN, bridges the gap between science and health across most platforms: major newspapers, magazines, books (Globesity), workshops, social media, and websites. In 2010, she launched www.ProbioticsNow.com to share the cascade of new discoveries in the microbiome. Always amazed at this "forgotten organ," Fleishman has also created white papers, blogs, videos, and social media for the International Probiotics Association. She recently published Fertility: Why Microbes, Weight & Nutrition Matter.
Vetted by the IPA Scientific Vetting Task force.